Armed with promising results from a primate study with a systemically delivered RNAi therapeutic, Alnylam Pharmaceuticals Inc. signed a research deal to access INEX Pharmaceuticals Corp.’s drug delivery technology.
The deal calls for the companies to evaluate Alnylam’s gene-silencing RNAi-based drugs delivered using INEX’s liposomal delivery platform. Cambridge, Mass.-based Alnylam will hold an option to exclusively license the technology for specific targets, in exchange for undisclosed license fees, as well as potential milestones and royalties.
"Alnylam decided it wanted to look at liposome delivery technology, and we are quite pleased that they desired to work with us," said Tim Ruane, president and CEO of INEX, which has designed a platform to encapsulate oligonucleotides, such as short interfering RNAs (siRNAs), into liposomes so that the two elements "work in tandem to actually drug the target and get the desired effect" of systemic administration.
Until recently, RNAi therapeutics had shown preclinical and early clinical success in indications in which they could be directly administered, such as Alnylam’s Phase I candidate, ALN-RSV01, for treating respiratory syncytial virus. That product is designed to be delivered directly to the lungs to silence the viral gene.
But the field of RNAi moved "a major step forward," with the publication in Nature of data demonstrating significant efficacy of a systemic RNAi therapeutic in silencing apolipoprotein B (apoB), a protein involved in cholesterol metabolism, said John Maraganore, president and CEO of Alnylam.
In that preclinical study, 18 non-human primates received siRNAs formed with liposomes delivered to liver cells. Data showed that, following a single intravenous bolus dose of the therapeutic, the RNAi-mediated mechanism of action effectively silenced more than 90 percent of the apoB mRNA expression with the top dose. In addition, Plasma apoB levels dropped by more than 75 percent, while cholesterol levels were reduced by more than 60 percent and LDL levels by more than 80 percent.
"The rapid onset and durability also were really surprising results," Maraganore told BioWorld Today. "Within 24 hours of a single administration, there were significant biological effects that last well beyond 11 days."
Treatment was well tolerated, though at the highest dosing levels investigators noticed a transient elevation of liver enzyme.
"But that’s reversible," Maraganore said. "And it may be related to the silencing of apoB itself."
Spurred by primate results, Alnylam is moving ahead with systemic RNAi programs, with plans to initiate clinical studies within the next 18 to 24 months.
While the Nature study focused on the apoB protein, the company has not yet disclosed which indication will be first in the clinic.
"Obviously, we have a lot of opportunities in front of us, such as viral diseases, metabolic disease, and cancer," Maraganore said, adding that the advantage of RNAi is its ability to hit previously undruggable targets.
What the Nature paper also reinforced was the promising use of liposomal technology to deliver the RNAi drug, and that "represented an attractive near-term strategy for systemic RNAi," Maraganore said.
The deal with INEX provides Alnylam with the intellectual property and capability "that INEX has built over many years with that technology," he added.
For INEX, the exercise of Alnylam’s option is dependent on the completion of its spin out into Tekmira Pharmaceuticals Corp., expected in the second quarter. In that reorganization, Tekmira will gain all of INEX’s targeted immunotherapy assets, including its liposomal program, and the company’s internal lead development product, INX-0167, in late preclinical development. (See BioWorld Today, Nov. 21, 2005.)
Earlier this month, INEX entered a deal to license three of its targeted chemotherapeutics, including Marqibo, to South San Francisco-based Hana Biosciences Inc. for up to $42 million. Marqibo received a not approvable letter in January 2005, after the FDA said Phase II data was insufficient for approval. (See BioWorld Today, March 20, 2006.)
"We’re staying quite busy right now," said INEX’s Ruane. "We’re supporting the Hana partnership, and now we’ve got the Alnylam partnership in the siRNA liposome delivery field."
Shares of INEX (TSE:IEX) gained C10 cents Monday to close at C59 cents (US50 cents).
In a separate agreement, Alnylam said it also will option liposome technology from the Massachusetts Institute of Technology. That technology is in the preclinical stage.
Alnylam’s stock (NASDAQ:ALNY) closed at $17.45 Monday, up 40 cents.